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Protein involved in hearing loss recovery

The snail-shaped cochlea is an organ in the inner ear that helps us to hear sounds. Within the cochlea, thousands of sensory cells known as hair cells are arranged in inner and outer rows.

Vibrations from sound waves cause these hair cells to move up and down and create an electrical signal that travels to the brain. Long or repeated exposure to loud noises can damage and even destroy hair cells. This noise-induced hearing loss can be permanent. Millions of Americans have noise-induced hearing loss.

Currently, devices such as assistive listening devices and hearing aids are used to help people with hearing loss. However, these don’t restore hearing and aren’t a cure. Because some people are more vulnerable than others to noise-induced hearing loss, researchers have sought to understand the genetic factors and mechanisms that may be protective. Ultimately, they hope these findings will lead to the development of treatments that can restore hearing.

A team led by Dr. Patricia White of the University of Rochester previously showed that a protein called Forkhead Box O3 (FOXO3) is expressed in both inner and outer hair cells. FOXO3 is a transcription factor—a type of protein that plays a role in gene regulation. Upon noise exposure, FOXO3 travels into the hair cell nucleus, suggesting it might play a role in the protective response to noise-induced damage. To test this hypothesis, the scientists used mice that had been genetically modified to lack the gene for FOXO3. The study was supported in part by NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD). Results were published on April 21, 2017, in Scientific Reports.

The scientists first explored the effect of noise on hearing. For 30 minutes, two-month-old mice were exposed to 105 decibels, equivalent to a personal stereo at maximum volume. Thirty-five mice had FOXO3 and 36 did not. Before the loud noise, both groups of mice had the same ability to hear the five high frequencies tested (8, 12, 16, 24, and 32 KHz). One day afterward, the researchers found that the mice lacking FOXO3 had become profoundly deaf. The mice with FOXO3 also had hearing loss, but it was far less severe. Two weeks afterward, the mice lacking FOXO3 continued to have severe hearing loss, but the normal mice seemed to mostly recover their hearing.

The team examined the effect of noise on structural damage to hair cells and other parts of the cochlea. They found that FOXO3 is needed for outer hair cell survival after loud noise. They linked the hearing loss in the FOXO3-deficient mice with outer hair cell loss and structural damage. Inner hair cells survived and appeared to be relatively undamaged. Finally, the scientists found FOXO3 in cochlear hair cells from a human cadaver, supporting the idea that it may also play a role in human hearing.

“Discovering that FOXO3 was important for the survival of outer hair cells is a significant advance,” White says. “We are also excited about the results because FOXO3 is a transcription factor, which regulates the expression of many target genes. We are currently investigating what its targets might be in the inner ear, and how they could act to protect the ear from damage."

White adds that they would also like to study whether increasing FOXO3 in cochlear hair cells would help protect against noise-induced hearing loss. “If it did, that could be very helpful for the active military as well as for people who work in noisy environments, such as miners,” she says.